Integrated mechanisms for corticostriatal control of action

The National Institute of Mental Health awarded Emory University $100,228 on December 30, 2026, under the Mental Health Research Grants program (CFDA 93.242) to support research on integrated mechanisms for corticostriatal control of action.

The award funds investigation of how the orbitofrontal cortex, premotor cortex, and dorsomedial striatum interact to coordinate exploration-exploitation decision-making—the balance between trying new strategies and leveraging proven approaches. The research builds on prior work identifying "memory trace" neurons in the orbitofrontal cortex that represent optimal reward-seeking strategies; inactivating these neurons during memory retrieval impairs mice's ability to recall and execute the best strategy to obtain reward. The project will define how the corticostriatal circuit implements action exploration or exploitation through chemogenetic and behavioral experiments examining OFC-to-M2 and M2-to-DMS projections and their role in conveying prior experience to drive reward-seeking behavior.

Work is performed in Atlanta, Georgia, with the period of performance running through July 5, 2029. Emory University's Office of Sponsored Programs serves as the recipient organization.

Abstract

One key challenge we face in day-to-day life is the explore/exploit dilemma: deciding whether to TRY new methods (exploration) or stick with proven strategies (exploitation). For instance, when conducting an experiment, one might choose between a familiar technique that has worked in the past or a new, less familiar approach. Understanding how our brains make these decisions is key to understanding how organisms can survive in complex and evolving environments. The orbitofrontal cortex (OFC), premotor cortex (M2), and dorsomedial striatum (DMS) appear to individually influence the balance between exploration and exploitation; however, IT is unclear whether or how these brain regions interact to coordinate this behavior. The goal of this proposal is to define how the OFC-M2-DMS circuit supports action exploration or exploitation. Recently, my lab identified specific "memory trace" neurons in the OFC that represent the best strategy to obtain a reward, allowing mice to exploit optimal actions in a changing reward context. Specifically, mice were trained to obtain foods using multiple response strategies, then reward likelihood decreased for one strategy and was maintained for another. Memory trace neurons are active when reward contingencies change, and again when mice must recall the best strategy to use when they seek food reward in the future (i.e., memory retrieval). Inactivating these trace neurons during memory retrieval impairs the ability of mice to recall the best strategy to obtain a reward, impairing exploitative behavior. Whether and how memory trace neurons interact with other brain regions to implement optimal reward-seeking strategies remains unclear. Previous studies have shown that chemogenetic inactivation of OFC-to-M2 projections blocks the capacity of mice to seek valued outcomes, and M2-to-DMS connections are thought to convey action-related aspects of prior experiences to drive behavior. Despite these findings, specific cell types, learning processes, and motor outputs have not been defined, in part because M2 is largely neglected in decision-making research. Aim 1 will determine how the OFC, including memory trace neurons in the OFC, interacts with M2 to allow mice to use optimal action strategies for exploitative behavior. I will use multi-site chemogenetic and FOS- targeted recombination in active populations (trap) techniques to address this question. Aim 2 will determine the outputs by which M2 coordinates the exploitation of optimal action strategies through projections to DMS. First, i will use chemogenetics to test whether M2-to-DMS connections are necessary for mice to exploit optimal action strategies. Then, i will use fiber photometry to record neural activity in the M2 and DMS in mice during exploitative behavior. Collectively, these aims will expand our understanding of the contribution of the circuitry between OFC, M2, and DMS to exploitative behavior. Completing these aims will enhance my current conceptual knowledge and skills, allow me to acquire new technical abilities, and develop the professional experience necessary to transition to postdoctoral training.